Alternative mRNA splicing events and regulators in epidermal differentiation
Shota Takashima,
Wujianan Sun,
Auke B.C. Otten,
Pengfei Cai,
Shaohong Isaac Peng,
Elton Tong,
Jolina Bui,
McKenzie Mai,
Oyumergen Amarbayar,
Binbin Cheng,
Rowen Jane Odango,
Zongkai Li,
Kun Qu,
Bryan K. Sun
Affiliations
Shota Takashima
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Wujianan Sun
Department of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Auke B.C. Otten
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Pengfei Cai
Department of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Shaohong Isaac Peng
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Elton Tong
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Jolina Bui
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
McKenzie Mai
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Oyumergen Amarbayar
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Binbin Cheng
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Rowen Jane Odango
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA
Zongkai Li
Department of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Kun Qu
Department of Oncology, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Bryan K. Sun
Department of Dermatology, University of California San Diego, La Jolla, CA 92109, USA; Corresponding author
Summary: Alternative splicing (AS) of messenger RNAs occurs in ∼95% of multi-exon human genes and generates diverse RNA and protein isoforms. We investigated AS events associated with human epidermal differentiation, a process crucial for skin function. We identified 6,413 AS events, primarily involving cassette exons. We also predicted 34 RNA-binding proteins (RBPs) regulating epidermal AS, including 19 previously undescribed candidate regulators. From these results, we identified FUS as an RBP that regulates the balance between keratinocyte proliferation and differentiation. Additionally, we characterized the function of a cassette exon AS event in MAP3K7, which encodes a kinase involved in cell signaling. We found that a switch from the short to long isoform of MAP3K7, triggered during differentiation, enforces the demarcation between proliferating basal progenitors and overlying differentiated strata. Our findings indicate that AS occurs extensively in the human epidermis and has critical roles in skin homeostasis.
